Blood concentrations of estradiol (E2) and testosterone (T); the metabolic clearance (MCR) and production rates (PR) of E2 and T; and the effects of dexamethasone suppression of E2 and t are examined in depressed pre- and postmenopausal women; depressed men, and non-depressed men and women. Preliminary results indicate that both pre-and postmenopausal depressed women, have abnormally elevated blood concentrations of E2 and T; significantly lower MCRs and PRs of E2; and significantly elevated MCRs and PRs of T. The reasons for the elevation of T and the reduction in PR E2 are unknown. Dexamethasone had little effect on either T or E2 of these women. Testosterone and E2 are antagonistic and their ratio to each other may affect their respective physiologic activities. The ratio of PR T to PR E2 in nondepressed premenopausal women is 1.4, the T to E2 PR ratio in depressed premenopausal women is 11.6. In order to achieve the T to E2 ratio of nondepressed women, our depressed women would have to increase their production of E2 10 fold. This imbalance may account for why depressed women require 10 to 20 times the normal dose of oral conjugated estrogens to relieve their symptoms of depression. Depressed men have significantly lower means of total plasma T and free T and significantly elevated levels of bound (non-physiologically active) T than nondepressed men. However, the MCR and PR of T are not significantly different in depressed and nondepressed men. The plasma E2 level of the depressed men is significantly elevated, but their E2 PR, while elevated, is not statistically different from nondepressed men, probably because of the small number of depressed patients. E2 is known to be antagonistic to the action of T. An imbalance in favor of E2 to T in depressed men might explain why the administration of T to depressed men resulted in a decrease in their symptoms of depression.